Through manipulating fluids using microfabricated channel and chamber structures, microfluidics is a powerful tool to realize high sensitive, high speed, high throughput, and low cost analysis. In addition, the method can establish a well-controlled microenvironment for manipulating fluids and particles. It also has rapid growing implementations in both sophisticated chemical/biological analysis and low-cost point-of-care assays. Some unique phenomena emerge at the micrometer scale. For example, reactions are completed in a shorter amount of time as the travel distances of mass and heat are relatively small; the flows are usually laminar; and the capillary effect becomes dominant owing to large surface-to-volume ratios. In the meantime, the surface properties of the device material are greatly amplified, which can lead to either unique functions or problems that would not be encountered at the macroscale. Also, each material inherently corresponds with specific microfabrication strategies and certain native properties of the device. Therefore, the material for making the device plays a dominating role in microfluidic technologies.
The ability to precisely forecast the fate of inhaled aerosols is necessary for the development of inhaled aerosolized drugs and assessing health threats of inhaled pollutant particles.
Until present, acinar flows have been commonly investigated using computational fluid dynamic (CFD) simulations and scaled-up experimental models based on hydrodynamic similarity matching. Computational approaches have considerably evolved over the past few decades: while examples of earlier acinar models comprised single alveoli or alveolated ducts, more recent models span across realistic acinar tree structures, featuring multiple generations of alveolated ducts. The growing body of numerical studies has suggested that a sequence of alveolar flow patterns co-exist along the acinar tree: the first proximal generations of the pulmonary acinar tree, characterized by a low ratio of alveolar to ductal flow rates (denoted as Qa/Qd), exhibit intricate recirculating flows inside the alveolus with irreversible fluid pathlines. In contrast, deeper acinar generations, where values of Qa/Qd gradually increase, exhibit more radial-like streamline configurations that yield quasi-reversible pathlines. In particular, simulations across multi-generation acinar trees agree with earlier predictions obtained using models of a single alveolus, when screening for values of the ratio Qa/Qd. Recently, direct lung imaging data of rat and mouse acini have led to the first CFD simulation of anatomically-based acinar flows. However, these studies have been limited to terminal alveolar sacs or a few alveoli surrounding a single duct. Yet, investigations of acinar flows are still largely driven by studies using generic alveolar geometries.
A number of experimental models incorporating a single alveolus or an alveolated duct have been reported (Chhabra and Prasad, 2011; Cinkotai, 1974; Karl et al., 2004; Tippe and Tsuda, 2000). In contrast to computational studies, however, experimental models of an acinar tree that also mimic expanding and contracting breathing motion have not been introduced so far. Such models remain critically needed both for validation of computational predictions and as investigative tools. To date, the scaled-up experiment with the largest number of acinar generations was introduced by Ma et al. (2009), featuring three acinar bifurcations lined with toroidal alveoli; however, the model was limited to studies under rigid wall conditions only. A more anatomically-realistic model was recently presented in a scaled-up silicone replica cast expanded by changes in pressure from the surrounding liquid in a closed chamber; however, the setup was limited to the last two generations of an acinar sac. In both instances, scaled-up experiments came short of capturing the hypothesized transition from recirculating to radial flows in the acinus, and thus did not confirm numerical predictions (Sznitman et al., 2009; Tsuda et al., 1995) of flow topologies hypothesized across pulmonary acinar trees. Another critical drawback with the use of scaled-up experiments lies in their limited ability to investigate particle transport and deposition due to the challenges in simultaneously matching the dimensionless numbers for flow and for particles.